The overall objectives of this program project application are to define and characterize the mechanisms of the bystander effect and to compare and contrast the nature of the signaling molecule(s) for the bystander effect versus genomic instability. Three well linked, fully integrated projects are proposed to address these issues and will be supported by the functions of the Technical Core. The main goals of the Technical Core include 1) Provide statistical and data analyses support to all the projects to ensure that uniform statistical methods will be used in all studies. 2) Provide experimental design support based on Monte Carlo simulation of input parameters from the three projects of this program project, to improve and optimize data acquisition. 3) Apply inverse modeling approaches to analyze the gene expression data generated in the projects, to provide insight into the underlying regulatory networks. 4) Provide expertise in the design and fabrication of special irradiation fixtures through the Instrument shop (Machine Shop) in our Center. 5) Provide support with respect to the daily operation of the accelerator based single-cell/ single-particle microbeam and also the stand-alone single-cell/ single-particle microbeam. Through collaborations with the Project Leaders of the individual projects, the Technical Core will facilitate the coordination of research efforts of this program project by a combination of experimental, theoretical and computational approaches.